{"title":"Bacterial effector OspB hijacks apoptosis through peptide-bond recombination of BH3 domain proteins.","authors":"Yue Shao, Dandan Yang, Xinguang Gao, Minghui Wang, Liyuan Meng, Tianye Niu, Li Xia, Jingjin Ding, Feng Shao, Yue Xu","doi":"10.1016/j.chom.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.chom.2025.09.018","url":null,"abstract":"<p><p>Apoptosis is a defense response involving key players, including BH3-only proteins that engage BCL-2 family proteins BAX and BAK, initiating mitochondrial outer membrane permeabilization and caspase activation. However, Shigella flexneri subverts these death pathways to promote infection. Here, we identify the Shigella type III secretion system effector OspB as an enzyme that suppresses apoptosis by targeting BAX and BAK. OspB recognizes BAX/BAK in complex with BH3-only activators, notably tBID, and catalyzes a peptide-bond recombination between their BH3 domains. This reaction generates chimeric proteins comprising the N-terminal BH3-only segment fused to the C-terminal region of BAX or BAK, irreversibly inhibiting protein function and thus mitochondrial outer membrane permeabilization and apoptosis. OspB-mediated apoptosis inhibition enhances S. flexneri virulence in vivo. Homologous effectors with similar catalytic activity are conserved across various bacterial species. These findings reveal a bacterial strategy for apoptosis inhibition via remodeling of BCL-2 family proteins, offering avenues for therapeutic intervention.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetically engineered plant endophytes broaden effector-triggered immunity.","authors":"Menglu Hou, Sitao Zhu, Ruixia Niu, Guitao Zhong, Zhao Wang, Ming Luo, Jiawei Long, Ruoying Yang, Zhijuan Tang, Shaosong Shi, Guoyong Xu","doi":"10.1016/j.chom.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.chom.2025.09.017","url":null,"abstract":"<p><p>Plants utilize nucleotide-binding leucine-rich repeat (NLR) receptors to detect pathogen effectors and initiate a potent immune response called effector-triggered immunity (ETI). However, this defense relies on the presence of recognizable effectors in pathogens, which is often unpredictable during natural infections. To address this, we engineer plant endophytes, termed Sentinels, to heterologously express effectors that are recognized by the host's corresponding NLR. Using an OxyR regulatory circuit, effector expression is activated by reactive oxygen species-a common signal during pathogen infection. This circuit enables ETI activation against pathogens without recognizable effectors. Colonization by the sentinel bacterium slightly alters microbial abundance but maintains overall microbiota diversity and normal plant growth. We demonstrate the strategy's versatility by testing distinct effector-NLR recognition pairs in various plants against a range of pathogens. This strategy exploits the microbiota-host-pathogen interaction network to rapidly engineer a spectrum-expanded ETI, complementing synthetic microbial consortia for plant defense.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Jacoby, Kaylie Scorza, Lia Ecker, Paola Nol Bernardino, Alexander S Little, Mary McMillin, Ramanujam Ramaswamy, Anitha Sundararajan, Ashley M Sidebottom, Huaiying Lin, Keith Dufault-Thompson, Brantley Hall, Xiaofang Jiang, Samuel H Light
{"title":"Gut bacteria metabolize natural and synthetic steroid hormones via the reductive OsrABC pathway.","authors":"Christian Jacoby, Kaylie Scorza, Lia Ecker, Paola Nol Bernardino, Alexander S Little, Mary McMillin, Ramanujam Ramaswamy, Anitha Sundararajan, Ashley M Sidebottom, Huaiying Lin, Keith Dufault-Thompson, Brantley Hall, Xiaofang Jiang, Samuel H Light","doi":"10.1016/j.chom.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.chom.2025.09.014","url":null,"abstract":"<p><p>Steroid hormone metabolism by the gut microbiome affects host physiology, however, the underlying microbial pathways remain incompletely understood. Here, we isolate a gut bacterial species, which we designate Clostridium steroidoreducens, that reduces cortisol and related steroid hormones to 3β,5β-tetrahydrosteroid products. Through transcriptomics and enzymatic discovery, we establish the C. steroidoreducens OsrABC steroid hormone pathway. OsrA is a 3-oxo-Δ<sup>1</sup>-steroid hormone reductase that targets synthetic glucocorticoids, including prednisolone-a frontline Crohn's disease therapy. OsrB is a 3-oxo-Δ⁴-steroid reductase that converts steroid hormones to 5β-dihydrosteroid intermediates, which OsrC subsequently reduces to 3β,5β-tetrahydro products. Homologs of osrA and osrB predict steroid-reducing activity across gut bacteria and are enriched in metagenomes of Crohn's disease patients. Consistent with a role in modulating drug efficacy, C. steroidoreducens colonization decreases prednisolone bioavailability in gnotobiotic mice. These findings thus define a previously unrecognized pathway for microbial steroid hormone inactivation and establish a mechanistic basis for bacterial interference with anti-inflammatory therapies.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":""},"PeriodicalIF":18.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Run to boost your gut microbiome that can help fight cancer.","authors":"Shuo Wang","doi":"10.1016/j.chom.2025.07.022","DOIUrl":"10.1016/j.chom.2025.07.022","url":null,"abstract":"<p><p>Exercise is beneficial to physical health, and it also helps to promote efficacy following immunotherapy. In a recent paper published in Cell, Phelps et al. identified that the gut microbiota plays a critical role in how exercise improves checkpoint inhibitor efficacy in melanoma.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"33 9","pages":"1464-1465"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magdalena Kujawska, David Seki, Lisa Chalklen, Jennifer Malsom, Raymond Kiu, Sara Goatcher, Ioulios Christoforou, Suparna Mitra, Lucy Crouch, Lindsay J Hall
{"title":"Host-specific microbiome and genomic signatures in Bifidobacterium reveal co-evolutionary and functional adaptations across diverse animal hosts.","authors":"Magdalena Kujawska, David Seki, Lisa Chalklen, Jennifer Malsom, Raymond Kiu, Sara Goatcher, Ioulios Christoforou, Suparna Mitra, Lucy Crouch, Lindsay J Hall","doi":"10.1016/j.chom.2025.08.008","DOIUrl":"10.1016/j.chom.2025.08.008","url":null,"abstract":"<p><p>Animals harbor divergent microbiota, including various Bifidobacterium species, yet their evolutionary relationships and functional adaptations remain understudied. Using samples from insects, reptiles, birds, and mammals, we integrated taxonomic, genomic, and predicted functional annotations to uncover how Bifidobacterium adapts to host-specific environments. Host phylogeny is a major determinant of gut microbial composition. Distinct microbiota in mammalian and avian hosts reflect evolutionary adaptations to dietary niches, such as carnivory, and ecological pressures. At a strain-resolved level, Bifidobacterium and their hosts exhibit strong co-phylogenetic associations, driven by vertical transmission and dietary selection. Functional analyses highlight striking host-specific adaptations in Bifidobacterium, particularly in carbohydrate metabolism and oxidative stress responses. In mammals, Bifidobacterium strains are enriched in glycoside hydrolases tailored to complex carbohydrate-rich diets, including multi-domain GH13_28 α-amylases associated with degradation of resistant starch. Together, these findings deepen our understanding of host-microbe co-evolution and the critical role of microbiota in shaping animal health and adaptation.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"33 9","pages":"1502-1517.e13"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Global currents, microbial footprints.","authors":"Jessika Füssel, Guillem Salazar, Lucas Paoli","doi":"10.1016/j.chom.2025.08.010","DOIUrl":"10.1016/j.chom.2025.08.010","url":null,"abstract":"<p><p>Marine microbial communities influence global biogeochemical cycles. In a recent Science issue, Kolody et al. integrated oceanographic measurements with high-resolution molecular sampling to show that hydrographic features shape the microbial functional landscape. Their findings highlight how physical ocean structure underpins microbial biogeography and its role in Earth system processes.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"33 9","pages":"1461-1463"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2025-09-10Epub Date: 2025-08-18DOI: 10.1016/j.chom.2025.05.020
Shally R Margolis, Alexander J Meeske
{"title":"Crosstalk between three CRISPR-Cas types enables primed type VI-A adaptation in Listeria seeligeri.","authors":"Shally R Margolis, Alexander J Meeske","doi":"10.1016/j.chom.2025.05.020","DOIUrl":"10.1016/j.chom.2025.05.020","url":null,"abstract":"<p><p>CRISPR-Cas systems confer adaptive immunity to their prokaryotic hosts through the process of adaptation, where sequences are captured from foreign nucleic acids and integrated as spacers in the CRISPR array, thereby enabling crRNA-guided interference against new threats. While the Cas1-2 integrase is critical for adaptation, it is absent from many CRISPR-Cas loci, rendering the mechanism of spacer acquisition unclear for these systems. In this study, we show that the RNA-targeting type VI-A CRISPR system of Listeria seeligeri acquires spacers from DNA substrates through the action of a promiscuous Cas1-2 integrase encoded by a co-occurring type II-C system, in a transcription-independent manner. We further demonstrate that the type II-C integration complex is strongly stimulated by preexisting spacers in a third CRISPR system (type I-B), which imperfectly match phage targets and prime type VI-A adaptation. Altogether, our results reveal an unprecedented degree of communication among CRISPR-Cas loci encoded by a single organism.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1550-1560.e4"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell host & microbePub Date : 2025-09-10Epub Date: 2025-08-18DOI: 10.1016/j.chom.2025.07.021
Leah M Smith, Peter C Fineran
{"title":"Type I CRISPR-Cas immunity primes type III spacer acquisition.","authors":"Leah M Smith, Peter C Fineran","doi":"10.1016/j.chom.2025.07.021","DOIUrl":"10.1016/j.chom.2025.07.021","url":null,"abstract":"<p><p>CRISPR-Cas systems are diverse, with microbes harboring multiple classes and subtypes. Type I DNA-targeting and type III RNA-targeting systems often co-occur, but their interactions remain unclear. Prodigiosinella has three CRISPR-Cas systems (I-E, I-F, and III-A) with independent adaptation machinery. Type III systems can trigger cell death, yet it is unknown how functional spacers are acquired. We found that type I interference generates substrates acquired by the type III adaptation machinery. Despite reducing type I interference efficiency, type III contributed to plasmid loss and provided an advantage when DNA-targeting systems failed. Type I priming influenced type III spacer length and source, with more spacers acquired near the type I target site. Invader DNA clearance by type I interference enabled retention of cytotoxic type III spacers that would otherwise be lost. This study reveals how RNA-targeting CRISPR-Cas systems function as a backup in multi-system hosts, bolstering population-level protection.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":" ","pages":"1561-1576.e6"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut bacteria help the brain with an oil change.","authors":"T Jaymie Connerly, Brittany D Needham","doi":"10.1016/j.chom.2025.08.003","DOIUrl":"10.1016/j.chom.2025.08.003","url":null,"abstract":"<p><p>In this issue, Huang et al. reveal a link between gut bacteria and recovery from brain damage. In a bacteria-dependent manner, a fatty acid \"oil\" improves microglial function through increased peroxisomes. This insight into microglia and their response to gut signals offers targets to explore brain health via gut modulation.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"33 9","pages":"1466-1467"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"All systems go: CRISPR crosstalk for enhanced immunity.","authors":"Kalani Gast, Rodolphe Barrangou","doi":"10.1016/j.chom.2025.08.002","DOIUrl":"10.1016/j.chom.2025.08.002","url":null,"abstract":"<p><p>In this issue of Cell Host & Microbe, companion manuscripts from Margolis & Meeske<sup>1</sup> and Smith & Fineran<sup>2</sup> demonstrate that CRISPR-Cas systems have an unprecedented level of cooperative crosstalk between different subtypes, which enables primed spacer acquisition. These studies illustrate how CRISPR-Cas systems cooperate to enhance adaptive immunity in bacteria.</p>","PeriodicalId":93926,"journal":{"name":"Cell host & microbe","volume":"33 9","pages":"1470-1472"},"PeriodicalIF":18.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}